Blood flow generation by the heart is the result of synchronized electromechanical myocardial events and fluid dynamics processes. Interactions between blood flow and the myocardium elicit the continuous remodeling of the heart, leading to flow patterns that minimize energy losses. The flow pattern in the normal left ventricle consists of a large diastolic vortex that channels the transit of blood towards the outflow tract. In a failing left ventricle, progressive adverse remodeling leads to abnormal flow patterns that are less efficient in channeling blood transit, and which may contribute further to the progression of heart failure. Thus, a deeper understanding of blood flow dynamics in normal and diseased left ventricles may provide insight on the pathophysiology of heart failure, leading to earlier diagnosis and improved treatment strategies of this syndrome. Recent years have witnessed a surge of interest in studying the role of flow patterns in blood transport inside the left ventricle. Despite significant advances, we still understand poorly how the fluid dynamical processes are synchronized with the electromechanical events to generate blood flow. Our preliminary studies suggest that the position and properties of diastolic vortices, and consequently, their ability to channel blood transit through the LV, are related to the timing of the myocardial events of the cycle. The goal of this research is to understand the dependence of the time evolution of the diastolic vortices on the duration of the left-ventricular filling phases, and to determine how this dependence affects blood flow transport and global ventricular function. In order to carry out the proposed research we have assembled an interdisciplinary team of investigators with complementary expertise ranging from cardiology, echocardiography and magnetic resonance imaging, to fluid dynamics, computational mechanics and image processing. We will validate and apply a novel echocardiographic modality to measure two-dimensional bi-directional time-resolved flow maps in the left ventricle in a group of patients undergoing cardiac resynchronization therapy at the UCSD Medical Center. We will use these measurements to determine the time evolution of diastolic vortices in these patients for different AV and VV delays, and characterize how these delays affect the transit of blood inside the left ventricle. We postulate that better knowledge of this dependence will increase our understanding of the benefits of cardiac resynchronization therapy. It will also improve current protocols for VV and AV optimization by improving patient selection and enabling LV contraction to take place under the most favorable hemodynamic conditions. PUBLIC HEALTH RELEVANCE: The proposed study aims to develop engineering technologies to non-invasively measure blood transport inside the left ventricle of patients undergoing cardiac resynchronization therapy, with the overarching goal of improving patient selection and optimization of this therapy.